Successive alterations of hippocampal gamma-aminobutyric acid B receptor subunits in a rat model of febrile seizure

• Published in: Life sciences (1973) 2006-05, Vol.78 (25), p.2944-2952
• Main Authors: Han, Ying, Qin, Jiong, Bu, Ding-Fang, Chang, Xing-Zhi, Yang, Zhi-Xian
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Blotting, Western; Disease Models, Animal; Febrile seizure; Gamma-aminobutyric acid; Hippocampus; Hippocampus - metabolism; Male; Protein Binding; Protein Subunits - metabolism; Rats; Rats, Sprague-Dawley; Receptor; Receptors, GABA-B - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Seizures, Febrile - metabolism
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2005.11.023

Febrile seizure (FS) is a frequently encountered seizure type in childhood. Changes of brain function following FS have clinical importance. The recently identified gamma-aminobutyric acid B receptor (GABA BR) is a metabotropic receptor of GABA. In this study, we used a rat model of recurrent FS to investigate the changes of GABA BR1a and GABA BR2 subunits in hippocampus after recurrent FS by using Western blot, quantitative RT-PCR, double immunofluorescence, in situ hybridization and immunoprecipitation/Western blot. After treatment of hyperthermia and the presence of induced seizures once every 2 days for 10 times, GABA BR1a and GABA BR2 subunits in hippocampus were decreased after 24 h of the last treatment. The decrease of GABA BR1a lasted for 15 days but that of GABA BR2 persisted for more than 30 days. The binding of GABA BR1a to GABA BR2 in hippocampus was also decreased significantly after 24 h of the last treatment and lasted for more than 30 days. In situ hybridization showed that GABA BR1a mRNA was significantly decreased in dentate gyrus, and GABA BR2 mRNA was considerably reduced in CA 3 region. In H 10 and FS 1 groups in which hyperthermia treatment was the same but no (H 10 group) or only one seizure (FS 1 group) was induced, the decrease of GABA BR1a and GABA BR2 subunits and the reduced binding capability between GABA BR1a and GABA BR2 subunits were also detected but with less severity, and the time recovering from these abnormalities was shorter. We conclude that GABA BR1a and GABA BR2 subunits and the binding of the 2 subunits decrease in hippocampus for a relatively long period of time after recurrent FS in immature rats. These changes may result in long-lasting imbalance of excitation/inhibition function in hippocampus, and are derived from the consequences of recurrent febrile seizures.